Young, urban minority women account for a growing number of new HIV/sexually transmitted infections (STIs), while prevention efforts are seriously lagging behind. Our overarching hypothesis is that efficacy of standard HIV interventions may be undermined in certain individuals by brain differences in the ability to make optimal in the heat of the moment risk decisions. In normal development, the reward-sensitive, impulse-driven brain of adolescence gradually becomes an adult brain with improved inhibition of reward impulses. This brain maturation, however, has a great deal of individual variability - and developmental delay (temporary or sustained) can result in a chronological adult with decision-making characteristics of an 'adolescent' brain. Based on our pilot dataset (n=142), we hypothesize that developmental delay may contribute to sub-optimal sexual decision-making (reflected in a cluster of risk behaviors - including early age of 1st sex, frequent unprotected sex, multiple sexual partners, multiple STIs) putting a subgroup of young women, at high sexual risk (HSR) for HIV. Do young women with this HSR phenotype indeed have a pattern of younger brain- behavioral vulnerabilities (BBVs are reward-relevant brain processes that can undermine optimal decision- making)? A between-groups design (HSR vs. low sexual risk, LSR) will recruit 18-24 year-old females from an urban family planning in a city with 5 times the national HIV rate with blacks accounting for 66% of new HIV cases. The study will compare BBVs for the HSR v LSR group in 4 domains with HIV risk-relevance (heightened reward sensitivity, greater risk taking and poor inhibition of reward impulses, and greater rejection sensitivity), using selected fMRI probes and behavioral tasks. The specific aim of our pioneering proof-of- concept R21 study is to determine whether young urban women with HSR have greater BBVs compared to those that have LSR. To accomplish this we will: A) Compare activation in a priori regions of the brain between those with HSR vs. LSR and~ B) Correlate brain activation patterns obtained in the on-scanner tasks with linked (off-scanner) behavioral scores. We hypothesize that those with HSR will evidence significantly greater vulnerability (greater response in a priori regions) in one or more domains relevant for HIV risk, and that behavioral scores will be significantly correlated with the brain activity in the specified a prior regions of interest, directly linking brain activity with the risk-relevant behavior. Our exploratoy aim is to characterize demographic, health and HIV risk behaviors of the HSR and LSR groups through survey assessment, providing an hypothesis-generating data-base for examining other potential associations (childhood trauma, partner violence, depression, cognitive ability) with our HIV risk-relevant brain data. Demonstrating a difference in BBVs for young women at HSR v. LSR for HIV and identifying the underlying brain processes would enable our long-term goals: to encourage a broader biologically-based understanding of HIV risk, and to open the way for new brain-targeted and/or brain-informed strategies for vulnerable individuals, with life-saving benefit. PUBLIC HEALTH RELEVANCE: The proposed research is relevant to public health because it may identify previously undetected brain vulnerabilities which can undermine optimal safer-sex decision-making and help explain why some young women are at especially high risk for acquiring HIV/STIs. The proposed research is relevant to NIH's mission because it may inform a new approach in HIV/STI prevention research with potential to improve the efficacy of existing HIV/STI prevention and/or generate novel biological and /or behavioral interventions.